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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
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Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
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Principles of Pharmacogenetics: Types of Genetic Variants01:27

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The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
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Pharmacogenomics Implementation: Considerations for Selecting a Reference Laboratory.

Teresa T Vo1, Gillian C Bell2, Aniwaa Owusu Obeng3,4

  • 1Department of Pharmacotherapeutics and Clinical Research, College of Pharmacy, University of South Florida, Tampa, Florida.

Pharmacotherapy
|July 13, 2017
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Summary
This summary is machine-generated.

Selecting the right clinical laboratory is crucial for pharmacogenomic testing implementation. Key factors include assay availability, variant coverage, support, and cost to ensure effective patient care.

Keywords:
clinical implementationpharmacogeneticspharmacogenomicsprecision medicine

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Area of Science:

  • Clinical Laboratory Science
  • Pharmacogenomics
  • Genetics

Background:

  • Implementing pharmacogenomics in patient care requires selecting suitable clinical laboratories for genetic testing.
  • Advances in genotyping technologies have led to widespread pharmacogenomic testing by clinical laboratories.

Purpose of the Study:

  • To provide practical considerations for selecting a clinical laboratory for pharmacogenomic testing.
  • To address the limited guidance currently available for this selection process.

Main Methods:

  • The study outlines practical considerations for selecting a clinical laboratory.
  • These considerations are broadly categorized into four domains: pharmacogene and variant selection, logistics, reporting of results, and test costs/reimbursement.

Main Results:

  • Selection criteria depend on internal vs. external assay availability, genomic variant coverage for the patient population, technical support, and cost.
  • Clinicians may be responsible for selecting reference laboratories for genomic interrogation.

Conclusions:

  • Guidance on selecting clinical laboratories for pharmacogenomic testing is limited.
  • This work offers a practical framework to aid in the selection of appropriate laboratories for pharmacogenomic assays.